On October 8, 1939, the commander of Piotrkow Trybunalski, Hans Drexler, created by decree a ghetto for the Jews in this central Polish town. The Piotrkow Ghetto is the first known ghetto to have been formed in occupied Poland. However, it took until late January 1940 to force the Jews to move there. The Judenrat issued several announcements ordering Jews to make this move, but since they did not have the desired impact, the Germans eventually evicted the Jews one by one from the “Aryan” quarter, ordered them to relocate to the ghetto, and transferred their vacated dwellings to Christians. Although Christian residents of the ghetto area were also ordered to leave their homes, many Poles lived or ran businesses there until the spring of 1942.

The ghetto was not fenced and its boundary was not guarded. Signs proclaiming the area a ghetto, bearing the likeness of skulls, were posted only near the ghetto boundaries and the main gate. The Jews were allowed to leave the ghetto without permits, albeit only at specified times of the day, and were allowed to spend longer periods of time on several "Aryan" streets. However, they were not allowed on the main streets. The Jewish curfew in the ghetto varied from order to order. An influx of refugees and displaced persons caused the ghetto population to swell from 10,000 at the beginning of the war to 16,500 in April 1942.